Exploring the relationship between genetic factors and outcome following brain injury has received increased attention in recent years. However, few studies have evaluated the influence of genes on specific sequelae of concussion. The purpose of this study was to determine how the ϵ4 allele of the apolipoprotein E (APOE) gene influences symptom expression following sports-related concussion. Participants included 42 collegiate athletes who underwent neuropsychological testing, including completion of the Post-Concussion Symptom Scale (PCSS), within 3 months after sustaining a concussion (73.8% were evaluated within 1 week). Athletes provided buccal samples that were analyzed to determine the make-up of their APOE genotype. Dependent variables included a total symptom score and four symptom clusters derived from the PCSS. Mann-Whitney U tests showed higher scores reported by athletes with the ϵ4 allele compared to those without it on the total symptom score and the physical and cognitive symptom clusters. Furthermore, logistic regression showed that the ϵ4 allele independently predicted those athletes who reported physical and cognitive symptoms following concussion. These findings illustrate that ϵ4+ athletes report greater symptomatology post-concussion than ϵ4- athletes, suggesting that the ϵ4 genotype may confer risk for poorer post-concussion outcome. (JINS, 2016, 22, 89–94)

Objectives: The aim of this study was to explore the relationship between cognitive and white matter deterioration in a group of participants with spinocerebellar ataxia type 2 (SCA2). Methods: Fourteen genetically confirmed participants with SCA2 and 14 aged-matched controls participated in the study. Diffusion tensor imaging tract-based spatial statistics were performed to analyze structural white matter integrity. Significant group differences in the mean diffusivity were correlated with SCA2 cognitive deficits. Results: Our analysis revealed higher mean diffusivity in the SCA2 group in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Cognitive scores correlated with white matter mean diffusivity in the parahippocampal area, inferior frontal and supramarginal gyri and the stria terminalis. Conclusions: Our findings show significant correlations between white matter microstructural damage in key areas affected in SCA2 and cognitive deficits. These findings result in a more comprehensive understanding of the effect of the neurodegenerative process in people with SCA2. (JINS, 2016, 22, 486–491)

Objectives: The present study explored the level of self-and informant reported executive functioning in daily living using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) in a large sample comprising healthy adults and patient cohorts with neurological and neuropsychiatric disorders. The relationship to neuropsychological test performance and self-reported emotional distress was explored, as well as the applicability of U.S. normative data. Methods: Scores on the self- and informant reported BRIEF-A are presented, along with scores on standardized cognitive tests, and on rating scales of self-reported emotional distress in a Norwegian healthy comparison group (n=115), patients with severe traumatic brain injury (n=125), focal frontal lobe damage (n=29), focal cerebellar lesion (n=24), Parkinson’s disease (n=42), attention deficit hyperactivity disorder (n=34), type II bipolar disorder (n=21), and borderline personality disorder (n=18). Results: Strong associations were observed between the BRIEF-A and emotional distress in both the healthy group and in neurological groups, while no or weak relationships with IQ and performance-based tests of executive function were seen. The relationship between BRIEF-A and emotional distress was weaker in the neuropsychiatric patient groups, despite high symptom load in both domains. Healthy participants tended to have BRIEF-A scores 1/2–3/4 SD below the U.S. normative mean of T score=50. Conclusions: The study demonstrates the need to interpret BRIEF-A results within a broad differential diagnostic context, where measures of psychological distress are included in addition to neuropsychological tests. Uncertainty about the appropriateness of U.S. normative data in non-U.S. countries adds to the need for interpretive caution. (JINS, 2016, 22, 682–694)

Objectives: One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of brain networks using graph theory and related these to GCA in healthy controls and individuals with schizophrenia. Methods: Participants (N=116 controls, 80 patients with schizophrenia) were recruited from four sites. GCA was represented by the first principal component of a large battery of neurocognitive tests. Graph metrics were derived from diffusion-weighted imaging. Results: The global metrics of longer characteristic path length and reduced overall connectivity predicted lower GCA across groups, and group differences were noted for both variables. Measures of clustering, efficiency, and modularity did not differ across groups or predict GCA. Follow-up analyses investigated three topological types of connectivity—connections among high degree “rich club” nodes, “feeder” connections to these rich club nodes, and “local” connections not involving the rich club. Rich club and local connectivity predicted performance across groups. In a subsample (N=101 controls, 56 patients), a genetic measure reflecting mutation load, based on rare copy number deletions, was associated with longer characteristic path length. Conclusions: Results highlight the importance of characteristic path lengths and rich club connectivity for GCA and provide no evidence for group differences in the relationships between graph metrics and GCA. (JINS, 2016, 22, 240–249)

Objectives: Behavioral variant frontotemporal dementia (bvFTD) is characterized by early atrophy in the frontotemporoinsular regions. These regions overlap with networks that are engaged in social cognition-executive functions, two hallmarks deficits of bvFTD. We examine (i) whether Network Centrality (a graph theory metric that measures how important a node is in a brain network) in the frontotemporoinsular network is disrupted in bvFTD, and (ii) the level of involvement of this network in social-executive performance. Methods: Patients with probable bvFTD, healthy controls, and frontoinsular stroke patients underwent functional MRI resting-state recordings and completed social-executive behavioral measures. Results: Relative to the controls and the stroke group, the bvFTD patients presented decreased Network Centrality. In addition, this measure was associated with social cognition and executive functions. To test the specificity of these results for the Network Centrality of the frontotemporoinsular network, we assessed the main areas from six resting-state networks. No group differences or behavioral associations were found in these networks. Finally, Network Centrality and behavior distinguished bvFTD patients from the other groups with a high classification rate. Conclusions: bvFTD selectively affects Network Centrality in the frontotemporoinsular network, which is associated with high-level social and executive profile. (JINS, 2016, 22, 250–262)